Update on the management of chronic rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is a common disorder characterized by mucosal inflammation of the nose and paranasal sinuses with sinonasal symptoms persisting for greater than 12 weeks. The etiology of CRS is incompletely understood. Current understanding supports inflammation, rather than infection, as the dominant etiologic factor. CRS significantly impacts patients’ quality of life and health care expenditure. There is no standard management of CRS. Treatment strategies differ based on divergent etiologies of the various CRS subclasses. Both systemic and topical agents are used. These interventions differ in CRS with nasal polyposis (CRSwNP), CRS without nasal polyposis (CRSsNP) and specific situations such as allergic fungal rhinosinusitis or aspirin-exacerbated respiratory disease. Antibiotics are the most commonly prescribed medication for CRS, but their role in management is not strongly supported by high-level studies. This paper provides a succinct review of the evidence supporting or refuting common therapeutic agents in the management of CRS. Novel and emerging strategies will also be discussed.

Chronic Rhinosinusitis and the Evolving Understanding of Microbial Ecology in Chronic Inflammatory Mucosal Disease

“…This is further compounded by difficulties in the definition of CRS itself, which is a heterogeneous group of conditions that share symptomatic expression but not necessarily underlying causative factors ( Fig. 3) (2,4,7,13,(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). This is particularly evident when we consider the range of comorbidities and complications associated with CRS, including polyposis, asthma, allergy, immunodeficiency, primary and secondary ciliary dyskinesia, gastroesophageal reflux disease, cystic fibrosis, aspirin hypersensitivity, and dental disease (2,7,13).…”

“…It is characterized by inflammation of the nasal and sinus mucosa (2,4) and may include nasal congestion or discharge, facial pain or pressure, loss of the sense of smell, polyposis, mucopurulent discharge, and edema or obstruction of the sinuses and nasal cavity (2,5). While acute rhinosinusitis (ARS) and subacute rhinosinusitis involve the resolution of symptoms within 4 and 12 weeks, respectively, progression to chronic rhinosinusitis (CRS), characterized by symptoms persisting for longer than 12 weeks, occurs in up to 5% of the general population (2,(5)(6)(7). CRS is a debilitating condition, with effects on quality of life being equal to or greater than those with chronic bronchitis, asthma, peptic ulcer disease, chronic obstructive pulmonary disease, congestive heart failure, and angina (2,(8)(9)(10).…”

“…Despite considerable research, the etiology of CRS remains poorly understood. A diverse range of factors have been investigated as potential causative agents, including infectious agents; aberrant inflammatory patterns; anatomic variations affecting the ostiomeatal complex (such as nasal septal deviation and concha bullosa) or sinonasal drainage abnormalities caused by aberrant frontal sinus cells; genetics underlying the innate immune system, such as epithelial barrier integrity and mucociliary clearance; and acquired disorders such as secondary ciliary dyskinesia, hypersensitivities associated with asthma, hormonal imbalance, autoimmune disorders, and immunodeficiency (5,7,13,14). Early research on CRS was principally based on an infection model of disease, with a focus on identifying a pathogenic microbial driver of the inflammatory response.…”

“…In recent years, however, an infection-based model of CRS has largely given way to an inflammation-based model, with the general focus shifting from possible causative pathogens to immunological factors that might underlie the disease process. Limited specific findings, together with a wealth of contradictions in the research to date, have led some to conclude that CRS may not be related to specific microbial taxa (or even microbial communities) (7,15) but rather that CRS is a purely immune-mediated disease in which microbial involvement may be limited to causing exacerbations. Nonetheless, interest in the microbiology of CRS continues to increase (Fig.…”

Prevention of sinonasal inflammation by a synthetic glycosaminoglycan

“…RS is an inflammatory respiratory disease that affects up to 16% of the United States population and is in dire need of new effective therapies. [23–31] We recently reported that intranasal administration of the inflammatory modulating peptide LL-37 causes profound sinonasal mucosal inflammation in the mouse with similar clinical signs to human RS,[32] as LL-37 causes cell death in the airways [33] and is elevated in sinus epithelial cells [34] and the nasal mucosa cultures of patients with RS. [35,36] Employing this model and based on prior evidence, we hypothesized that GM-0111 would (1) effectively coat and penetrate the sinuses through topical, intranasal delivery and (2) prevent sinonasal inflammation by protecting the sinonasal epithelium against inflammatory cell infiltration and cell death.…”